Xin-Xiang Li1, Lei Liang1, Li-Yong Huang1, San-Jun Cai1. 1. Xin-Xiang Li, Lei Liang, Li-Yong Huang, San-Jun Cai, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Abstract
AIM: To review and assess the evidence related to cetuximab treatment in metastatic colorectal cancer (mCRC) with regard to KRAS status. METHODS: PubMed, EMBASE, Cochrane database and American Society of Clinical Oncology meeting abstracts were searched for randomized controlled trials (RCTs) reporting the effect of KRAS status on efficacy of chemotherapy regimen with or without cetuximab in mCRC. Baseline information such as sex and age was summarized from the included studies. Hazard ratios of progression-free survival (PFS) and overall survival (OS) as well as objective response based on KRAS status were extracted for analysis. RESULTS: A total of 8 RCTs with 6780 patients were included. The combined analysis showed that cetuximab failed to improve the OS and PFS in patients with mCRC. However, in subgroup analysis, the pooled data showed that addition of cetuximab to irinotecan containing chemotherapy regimen was sufficient to improve OS and PFS in wild-type KRAS mCRC patients, but not in patients with mutant-type KRAS. The addition of cetuximab increased the incidence of adverse events such as diarrhea, rash, skin toxicity/rash, and nausea and vomiting. There was no significant publication bias existing in the included studies. CONCLUSION: The clinical benefit of cetuximab was only confirmed in patients with wild-type KRAS. KRAS status could be considered a biomarker of efficacy of cetuximab.
AIM: To review and assess the evidence related to cetuximab treatment in metastatic colorectal cancer (mCRC) with regard to KRAS status. METHODS: PubMed, EMBASE, Cochrane database and American Society of Clinical Oncology meeting abstracts were searched for randomized controlled trials (RCTs) reporting the effect of KRAS status on efficacy of chemotherapy regimen with or without cetuximab in mCRC. Baseline information such as sex and age was summarized from the included studies. Hazard ratios of progression-free survival (PFS) and overall survival (OS) as well as objective response based on KRAS status were extracted for analysis. RESULTS: A total of 8 RCTs with 6780 patients were included. The combined analysis showed that cetuximab failed to improve the OS and PFS in patients with mCRC. However, in subgroup analysis, the pooled data showed that addition of cetuximab to irinotecan containing chemotherapy regimen was sufficient to improve OS and PFS in wild-type KRAS mCRC patients, but not in patients with mutant-type KRAS. The addition of cetuximab increased the incidence of adverse events such as diarrhea, rash, skin toxicity/rash, and nausea and vomiting. There was no significant publication bias existing in the included studies. CONCLUSION: The clinical benefit of cetuximab was only confirmed in patients with wild-type KRAS. KRAS status could be considered a biomarker of efficacy of cetuximab.
Entities:
Keywords:
Cetuximab; KRAS; Meta-analysis; Metastatic colorectal cancer; Standard chemotherapy
Authors: C Bokemeyer; I Bondarenko; J T Hartmann; F de Braud; G Schuch; A Zubel; I Celik; M Schlichting; P Koralewski Journal: Ann Oncol Date: 2011-01-12 Impact factor: 32.976
Authors: Eric Van Cutsem; Claus-Henning Köhne; István Láng; Gunnar Folprecht; Marek P Nowacki; Stefano Cascinu; Igor Shchepotin; Joan Maurel; David Cunningham; Sabine Tejpar; Michael Schlichting; Angela Zubel; Ilhan Celik; Philippe Rougier; Fortunato Ciardiello Journal: J Clin Oncol Date: 2011-04-18 Impact factor: 44.544
Authors: Dominik P Modest; Thomas Brodowicz; Sebastian Stintzing; Andreas Jung; Jens Neumann; Ruediger P Laubender; Janja Ocvirk; Galina Kurteva; Zsuzsanna Papai; Regina Knittelfelder; Thomas Kirchner; Volker Heinemann; Christoph C Zielinski Journal: Oncology Date: 2012-08-29 Impact factor: 2.935
Authors: Young Kwang Chae; Keerthi Ranganath; Peter S Hammerman; Christos Vaklavas; Nisha Mohindra; Aparna Kalyan; Maria Matsangou; Ricardo Costa; Benedito Carneiro; Victoria M Villaflor; Massimo Cristofanilli; Francis J Giles Journal: Oncotarget Date: 2017-02-28